A5016773382- Ion channel regulation and function
- Neuroscience and Neuropharmacology Research
- Neuroscience and Neural Engineering
- Cardiac electrophysiology and arrhythmias
- Neurobiology and Insect Physiology Research
- bioluminescence and chemiluminescence research
- DNA and Nucleic Acid Chemistry
- Nitric Oxide and Endothelin Effects
- Radical Photochemical Reactions
- Photoreceptor and optogenetics research
- Protein Kinase Regulation and GTPase Signaling
- Advanced Fluorescence Microscopy Techniques
- Molecular Sensors and Ion Detection
- Advanced biosensing and bioanalysis techniques
- Retinal Development and Disorders
- Receptor Mechanisms and Signaling
- Neural dynamics and brain function
- Mechanisms of cancer metastasis
- Metabolism and Genetic Disorders
- Alcoholism and Thiamine Deficiency
- Diet and metabolism studies
- Eicosanoids and Hypertension Pharmacology
- Plant nutrient uptake and metabolism
- Biotin and Related Studies
- Malaria Research and Control
UCB Pharma (Belgium)
2022-2023
Brandeis University
2017-2019
Institut Interdisciplinaire de Neuroscience
2017
Université de Bordeaux
2010-2017
Portland State University
2014
Rush University
2005-2013
Rush University Medical Center
2008-2009
Universidade de São Paulo
2000-2004
The role of calcium in signal transduction relies on the precise spatial and temporal control its concentration. existing means to detect fluctuations Ca2+ concentrations with adequate resolution are limited. We introduce here a method measure defined locations living cells that is based linking Ca2+-sensitive dye Indo-1 SNAP-tag fusion proteins. Fluorescence spectroscopy SNAP-Indo-1 conjugates vitro showed retained Ca2+-sensing ability Indo-1. In proof-of-principle experiment, local sensing...
Ca 2+ signals, produced by release from cellular stores, switch metabolic responses inside cells. In muscle, sparks locally exhibit the rapid start and termination of cell-wide signal. By imaging store using shifted excitation emission ratioing fluorescence, a surprising observation was made: Depletion during or voltage-induced occurs too late, continuing to progress even after channels have closed. This finding indicates that is released “proximate” compartment functionally in between lumen...
To activate skeletal muscle contraction, action potentials must be sensed by dihydropyridine receptors (DHPRs) in the T tubule, which signal Ca 2+ release channels or ryanodine (RyRs) sarcoplasmic reticulum (SR) to open. We demonstrate here an inhibitory effect of tubule on production sparks release. Murine primary cultures were confocally imaged for detection and visualization. After 72 h differentiation, tubules extended from periphery less than one-third myotube radius. Spontaneous found...
Stimuli are translated to intracellular calcium signals via opening of inositol trisphosphate receptor and ryanodine (RyR) channels the sarcoplasmic reticulum or endoplasmic reticulum. In cardiac skeletal muscle amphibians stimulus is depolarization transverse tubular membrane, transduced by voltage sensors at tubular–sarcoplasmic junctions, unit signal Ca 2+ spark, caused concerted multiple RyR channels. Mammalian muscles instead lose postnatally ability produce sparks, they also RyR3, an...
The mechanisms that terminate Ca2+ release from the sarcoplasmic reticulum are not fully understood. D4cpv-Casq1 (Sztretye et al. 2011. J. Gen. Physiol. doi:10.1085/jgp.201010591) was used in mouse skeletal muscle cells under voltage clamp to measure free concentration inside (SR), [Ca2+]SR, simultaneously with cytosol, [Ca2+]c, during response long-lasting depolarization of plasma membrane. ratio flux (derived [Ca2+]c(t)) over gradient drives it (essentially equal [Ca2+]SR) provided...
Plasmepsin X (PMX) is an essential aspartyl protease controlling malaria parasite egress and invasion of erythrocytes, development functional liver merozoites (prophylactic activity), blocking transmission to mosquitoes, making it a potential multistage drug target. We report the optimization binding scaffold discovery potent, orally active PMX inhibitors with in vivo antimalarial efficacy. Incorporation safety evaluation early characterization precluded compounds long human half-life (t1/2)...
Intracellular calcium signals regulate multiple cellular functions. They depend on release of Ca2+ from stores into the cytosol, a process that appears to be tightly controlled by changes in [Ca2+] within store. A method image free organelles was devised, which provided first quantitative confocal images inside sarcoplasmic reticulum (SR) skeletal muscle. The exploits, for greater sensitivity, dual spectral shifts some fluorescent dyes undergo upon binding Ca2+. It implemented with...
Intracellular calcium signals regulate multiple cellular functions. They depend on release of Ca(2+) from stores into the cytosol, a process that in many types cells appears to be tightly controlled by changes [Ca(2+)] within store. In contrast with cardiac muscle, where depletion sarcoplasmic reticulum is crucial determinant termination release, skeletal muscle there no agreement regarding sign, or even existence an effect SR level release. To address this issue we measured transients mouse...
Contractile activation in striated muscles requires a Ca2+ reservoir of large capacity inside the sarcoplasmic reticulum (SR), presumably protein calsequestrin. The buffering power calsequestrin vitro has paradoxical dependence on [Ca2+] that should be valuable for function. Here, we demonstrate this is present living cells. signals elicited by membrane depolarization under voltage clamp were compared single skeletal fibers wild-type (WT) and double (d) Casq-null mice, which lack both...
Current fluorescent monitors of free [Ca2+] in the sarcoplasmic reticulum (SR) skeletal muscle cells are limited quantitative value. They provide either a nonratio signal that is difficult to calibrate and not specific or, case Forster resonant energy transfer (FRET) biosensors, small dynamic range, which may be degraded further by imperfect targeting interference from endogenous ligands calsequestrin. We describe novel tool uses cameleon D4cpv, has greater range lower susceptibility than...
Malignant hyperthermia (MH) is linked to mutations in the type 1 ryanodine receptor, RyR1, Ca2+ channel of sarcoplasmic reticulum (SR) skeletal muscle. The Y522S MH mutation was studied for its complex presentation, which includes structurally and functionally altered cell 'cores'. Imaging cytosolic intra-SR [Ca2+] muscle cells heterozygous YS mice we determined release flux activated by clamp depolarization, permeability (P) SR membrane (ratio gradient) buffering power (B). In resting...
Sensory experience plays an important role in shaping neural circuitry by affecting the synaptic connectivity and intrinsic properties of individual neurons. Identifying molecular players responsible for converting external stimuli into altered neuronal output remains a crucial step understanding experience-dependent plasticity circuit function. Here, we investigate activity-regulated, non-canonical Ras-like GTPase Rem2 visual plasticity. We demonstrate that Rem2-/- mice fail to exhibit...
Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a well-characterized, abundant that regulates diverse set of functions in tissue-specific manner. For example, heart muscle, CaMKII Ca2+ homeostasis, whereas neurons, activity-dependent dendritic remodeling and long-term potentiation (LTP), neurobiological correlate learning memory. Previously, we identified the GTPase Rem2 as critical regulator dendrite branching homeostatic plasticity vertebrate nervous system. Here, report directly...
Peroxynitrite is shown here to promote the aerobic oxidation of isobutanal (IBAL) and 3-methyl-2,4-pentanedione (MP) in a pH 7.2 phosphate buffer into acetone plus formate biacetyl acetate, respectively. These products are expected from dioxetane intermediates, whose thermolysis known be chemiluminescent (CL). Accordingly, extent total oxygen uptake by IBAL at different concentrations parallels corresponding CL maximum intensities. The profile based on data for MP reaction matches titration...
In the framework of IMI2-NeuroDeRisk consortium, three in vitro electrophysiology assays were compared to improve preclinical prediction seizure-inducing liabilities. Two cell models, primary rat cortical neurons and human induced pluripotent stem (hiPSC)-derived glutamatergic co-cultured with hiPSC-derived astrocytes tested on two different microelectrode array (MEA) platforms, Maestro Pro (Axion Biosystems) Multiwell-MEA-System (Multi Channel Systems), separate laboratories....
Oxidative stress is believed to play a role in the pathogenesis of several diseases, including diabetes and inborn errors metabolism. The types oxidative damage observed these pathologies have been attributed excessive production reactive intermediates relating accumulation toxic metabolites. extremely oxidizing peroxynitrite can also be high pathologies. We study here oxidation initiated by ethyl esters acetoacetate (EAA) 2-methylacetoacetate (EMAA), metabolites that accumulate...
GABA
Hereditary tyrosinemia type I (HT1) is an inborn metabolic error characterized by hepatorenal dysfunction. Affected patients excrete large quantities of succinylacetone (SA), a tyrosine catabolite believed to be involved in the pathogenesis HT1. A growing body evidence relates oxidative stress observed disorders free radicals generated from accumulated metabolites. In this context, oxidation SA peroxynitrite or cytochrome c yielding reactive intermediates and products was investigated here....
Abstract CaMKII is a well-characterized, abundant protein kinase that regulates diverse set of functions in tissue specific manner. For example, heart muscle, Ca 2+ homeostasis while neurons activity-dependent dendritic remodeling and Long Term Potentiation (LTP), biological correlate learning memory. Previously, we identified the noncanonical GTPase Rem2 as critical regulator dendrite branching synapse formation vertebrate nervous system. Here, report directly interacts with potently...